MMP‐9 gene rs3918242 polymorphism increases risk of stroke: A meta‐analysis

Wang, Baohua; Wang, Yinhua; Zhao, Lei

doi:10.1002/jcb.27299

Cited by 17 publications

(14 citation statements)

References 25 publications

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“…Contrary, another metaanalysis suggested that MMP-9 (-1562C/T) polymorphisms might be a risk factor for ischemic stroke [36]. Also, several recent studies have reported the significant association between MMP-9 and cerebral ischemic stroke [15,37,38]. Gao et al [37] showed that the rs3787268 locus in the MMP-9 gene might increase the risk of ischemic stroke in a southern Chinese Han population.…”

Section: Discussionmentioning

confidence: 99%

Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?

Zhao¹,

Yang²,

Xue³

et al. 2022

J. Integr. Neurosci.

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Background: Matrix metalloproteinase-9 (MMP-9) is a significant protease required for synaptic plasticity, learning, and memory. Yet, the role of MMP-9 in the occurrence and development of cognitive decline after ischemic stroke is not fully understood. In this study, we used clinical data experiments to further investigate whether MMP-9 and genetic polymorphism are associated with poststroke cognitive impairment or dementia (PSCID). Materials and Methods: A total of 148 patients with PSCID confirmed by the Montreal Cognitive Assessment (MoCA) 3 months after onset (PSCID group) were included in the study. The MMP-9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism, and the serum level of MMP-9 was measured using enzyme-linked immunosorbent assay (ELISA). The same manipulations have been done on 169 ischemic stroke patients without cognitive impairment (NCI group) and 150 normal controls (NC group). Results: The expression level of serum MMP-9 in the PSCID group and NCI group was higher compared to the NC group, and the levels in the PSCID group were higher than that in the NCI group (all p < 0.05). Diabetes mellitus, hyperhomocysteinemia, and increased serum MMP-9 levels were the main risk factors of cognitive impairment after ischemic stroke. The serum level of MMP-9 was negatively correlated with the MoCA score, including visual-spatial executive, naming, attention, language, and delayed recall. Genetic polymorphism showed that TC genotype with MMP-9 rs3918242 and CC genotype were associated with a significantly increased risk of PSCID; moreover, the TC genotype significantly increased the risk of cognitive impairment. In the TCCC genotype of MMP-9 rs3918242, diabetes mellitus and hyperhomocysteinemia were associated with the increased risk of PSCID; also, hyperhomocysteinemia could increase the risk of cognitive impairment. Conclusions: MMP-9 level and MMP-9 rs3918242 polymorphism have an important role in the occurrence and development of post-stroke cognitive impairment or dementia (PSCID).

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Section: Discussionmentioning

confidence: 99%

Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?

Zhao¹,

Yang²,

Xue³

et al. 2022

J. Integr. Neurosci.

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“…The work is also limited by relatively low patient number and potentially biased by the absence of a matched nondiabetic cohort to investigate whether this relationship applies only in the context of diabetes. Furthermore, while the minor T allele of rs3918242 is associated with coronary artery and cerebrovascular diseases in large clinical studies and a recent meta-analysis, [20,27,28] it has not emerged in GWAS of vascular diseases to date. However, in order to reduce the likelihood of false positive results due to multiple testing, current GWAS require p-values in the order of 10 -8 and consequently identify only a minority of gene variants associated with disease risk.…”

Section: Discussionmentioning

confidence: 99%

Investigation of association of genetic variant rs3918242 of matrix metalloproteinase-9 with hypertension, myocardial infarction and progression of ventricular dysfunction in Irish Caucasian patients with diabetes: a report from the STOP-HF follow-up programme

Watson

Spiers

Waterstone

et al. 2021

BMC Cardiovasc Disord

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Background Hypertension and/or myocardial infarction are common causes of heart failure in Type 2 diabetes. Progression to heart failure is usually preceded by ventricular dysfunction, linked to matrix metalloproteinase (MMP) mediated extracellular matrix changes. We hypothesise that the minor allele of genetic variant rs3918242 in the promoter region of the MMP-9 gene is associated with hypertension and/or myocardial infarction, with resultant progression of dysfunctional cardiac remodelling in patients with diabetes without symptomatic heart failure. Methods We genotyped 498 diabetes patients participating in the St Vincent’s Screening TO Prevent Heart Failure (STOP-HF) follow-up programme for the rs3918242 single nucleotide polymorphism and investigated associations with the co-primary endpoints hypertension and/or myocardial infarction using a dominant model. We also evaluated resulting cardiometabolic phenotype and progression of ventricular dysfunction and cardiac structural abnormalities over a median follow-up period of 3.5 years. Results The CT/TT genotype comprised 28.1% of the cohort and was associated with a twofold higher risk of myocardial infarction (17.9% vs 8.4%), a reduction in ejection fraction and greater left ventricular systolic dysfunction progression [adjusted OR = 2.56 (1.09, 6.01), p = 0.026] over a median follow-up of 3.5 years [IQR 2.6, 4.9 years]. Conversely, rs3918242 was not associated with hypertension, blood pressure, pulse pressure or left ventricular mass index at baseline or over follow up. Conclusions Diabetes patients with the minor T allele of rs3918242 in the STOP-HF follow up programme have greater risk of myocardial infarction, lower ejection fraction and greater progression of left ventricular systolic abnormalities, a precursor to heart failure. These data may support further work on MMP-9 as a biomarker of ventricular dysfunction and the investigation of MMP-9 inhibitors for heart failure prevention in diabetes, particularly in the post-infarction setting. ClinicalTrials.gov Identifier: NCT00921960

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“…Epidemiological analysis shows genetic factors play a crucial role in IS susceptibility ( 2 , 6 ), accounting for 50% ( 10 ). Therefore, there is an urgent need to study the genetic variants associated with the occurrence of IS ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

“…Vascular inflammation is a key factor in IS ( 11 ). Inflammation can not only promote thrombus formation and improve the stability of thrombus, but also damage the blood-brain barrier (BBB) ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

“…Inflammation can not only promote thrombus formation and improve the stability of thrombus, but also damage the blood-brain barrier (BBB) ( 12 ). Matrix metalloproteinases (MMPs), as a class of proteolytic zinc-dependent enzymes, can regulate cytokines ( 13 ), angiogenesis ( 10 ), extracellular matrix (ECM) degradation ( 14 ), and cause BBB disorders ( 4 ), which affect the pathogenesis of vascular inflammation, stroke and atherosclerosis ( 11 ). It has been reported that the MMPs associated with IS were mainly concentrated in MMP2 and MMP9 ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Impact of MMP2 rs243849 and rs14070 genetic polymorphisms on the ischemic stroke susceptibility in Chinese Shaanxi population

Yang

Zhang

et al. 2022

Front. Neurol.

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BackgroundIschemic stroke (IS) is a complex neurological disease affected by genetics and environment. Matrix metalloproteinase-2 (MMP2) is involved in extracellular matrix (ECM) degradation, inflammation and angiogenesis to regulate the development and recovery of IS.PurposesThe aim of this study was to explore the association of rs1053605, rs243849 and rs14070 in MMP2 with the risk of IS in Chinese Shaanxi population.MethodsIn this study, 677 IS patients and 681 normal controls were recruited. Rs1053605, rs243849 and rs14070 in MMP2 were genotyped. Logistic regression analysis was applied to evaluate the association of rs1053605, rs243849 and rs14070 in MMP2 with IS susceptibility and the association of environmental factors with MMP2 genetic susceptibility to IS.ResultsThe results of the overall analysis demonstrated that rs14070 in MMP2 significantly reduced the risk of IS in Chinese Shaanxi population (OR = 0.767, 95% CI = 0.619–0.952, P = 0.016). Subgroup analysis illustrated that rs243849 in MMP2 evidently increased the risk of IS among drinkers, while rs14070 in MMP2 apparently reduced IS susceptibility among females, participants with aged >55, smokers and drinkers.ConclusionsCollectively, rs243849 and rs14070 in MMP2 were significantly associated with the risk of IS in Chinese Shaanxi population, and the effect of MMP2 to IS may be associated with its genetic susceptibility.

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MMP‐9 gene rs3918242 polymorphism increases risk of stroke: A meta‐analysis

Cited by 17 publications

References 25 publications

Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?

Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?

Investigation of association of genetic variant rs3918242 of matrix metalloproteinase-9 with hypertension, myocardial infarction and progression of ventricular dysfunction in Irish Caucasian patients with diabetes: a report from the STOP-HF follow-up programme

Impact of MMP2 rs243849 and rs14070 genetic polymorphisms on the ischemic stroke susceptibility in Chinese Shaanxi population

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